Genetic analysis of the TBX1 gene promoter in indirect inguinal hernia

Inguinal hernia is a common disease, most cases of which are indirect inguinal hernia (IIH). Genetic factors play an important role for inguinal hernia. Increased incidences of inguinal hernia have been reported in patients with 22q11.2 microdeletion syndrome, which is mainly caused by TBX1 gene mutations. Thus, we hypothesized that altered TBX1 gene expression may contribute to IIH development. In this study, the human TBX1 gene promoter was genetically analyzed in children with IIH (n=100) and ethnic-matched controls (n=167). Functions of DNA sequence variants (DSVs) within the TBX1 gene promoter were examined in cultured human fibroblast cells. The results showed that two heterozygous DSVs were found, both of which were single nucleotide polymorphisms. One DSV, g.4248 C>T (rs41298629), was identified in a 2-year-old boy with right-sided IIH, but not in all controls, which significantly decreased TBX1 gene promoter activity. Another DSV, g.4199 C>T (rs41260844), was found in both IIH patients and controls with similar frequencies (P>0.05), which did not affect TBX1 gene promoter activity. Collectively, our data suggested that the DSV within the TBX1 gene promoter may change TBX1 level, contributing to IIH development as a rare risk factor. Underlying molecular mechanisms need to be established.